The present invention relates to a new and improved method of, and circuit for, generating measuring pulses in a particle analyzer for the analysis of particles suspended in a liquid, especially for the analysis of blood cells.
The equipment of the present development is generally of the type comprising a conductivity or measuring cell, the impedance of which between two terminals of the conductivity cell changes upon passage of a particle through the conductivity cell. Further, there is provided a controllable current supply for supplying the conductivity cell with a current which is regulated for maintaining a reference value corresponding to a control value. A receiver acting as a high-pass filter and having high input impedance serves for the essentially currentless removal of a potential or voltage between the terminals of the conductivity cell and for the formation of a receiver signal which corresponds to such components of such potential whose frequency lies above a threshold or cut-off frequency corresponding to the high-pass filter.
As already mentioned the invention relates to circuitry for producing measuring pulses in a particle analyzer for the analysis of particles suspended in a liquid, especially particles in the form of blood cells, and which apparatus comprises a conductivity or measuring cell having at least two terminals, between which there can be measured a change in impedance upon passage of a particle through the conductivity cell. There is also provided a controllable current supply having a control input and two output terminals, wherein each respective one is connected with a respective terminal of the conductivity cell. There is also provided a receiver composed of a combination of an amplifier having high input impedance and a high-pass filter having an appropriate threshold or cut-off frequency.
Now from Swiss Pat. No. 420,669 there is known to the art, by way of example, a current source which delivers a constant direct-current and a receiver whose input impedance for direct-current is extremely high and, on the other hand, is extremely low for alternating-current or pulses above a predetermined threshold or cut-off frequency. If with such type equipment a particle passes through the conductivity cell, then there is produced in the conductivity cell a pulse-like change of the impedance, whereupon there is branched-off from the conductivity cell an appropriate part of the current delivered by the current source and delivered to the receiver. In the receiver the branched-off current part is detected as a measuring pulse. The volume of the particles which are to be analyzed is proportional to the relative change of the impedance of the conductivity cell during passage of a particle. However, with this equipment the measuring pulse is only approximately proportional to the relative change of the impedance of the conductivity cell, since the proportionality is only valid to the extent that the branched-off current part remains negligibly small in comparison to the total current delivered by the current source. In order to fulfill this condition a rather high current must flow through the conductivity cell. This, in turn, causes disadvantageous electrochemical and thermal side effects, for instance a polarization of the electrodes of the conductivity cell, formation of bubbles at the electrodes, heating-up of the liquid, and a delay in maintaining the equilibrium state of the conductivity cell after placing the equipment into operation.
Also it is known, for instance, from Swiss Pat. No. 546,437 to maintain small enough yet constant the current flowing through the conductivity cell and at the same time to insure for the desired proportionality of a measuring pulse with regard to the relative change of the impedance of the conductivity cell. For this purpose the receiver is designed to have a high input impedance. At the terminals of the conductivity cell there are measured voltage pulses, and the direct-current voltage applied to the conductivity cell, i.e., the quiescent value of the voltage is maintained constant with the conductivity cell free of particles. With constant current the quiescent or static voltage is markedly dependent upon the temperature of the liquid, so that there is contemplated a control of the current source in order to maintain constant the quiescent voltage without causing disappearance of the voltage pulses to be measured. For this purpose the control of the current source has a time-constant, so that it only responds to such voltage changes whose frequency spectrum is below a predetermined threshold frequency. It is assumed that the temperature-dependent changes of the impedance of the conductivity cell take place much more slowly than the changes of such impedance which are brought about during through-passage of a particle. What is disadvantageous with this solution is that the quiescent current flowing through the conductivity cell free of particles only can be influenced by means of the value of a reference potential or voltage which controls the control device or control. The current is intentionally maintained temperature-dependent, however the desired and therefore strived for result is not achieved, because the current-voltage characteristic of the measuring cell is not linear. Furthermore, during the course of the same working day it can happen that the quiescent current periodically is optimum, but however periodically is too small or too great.
Now in the same Swiss Pat. No. 546,437 it is proposed to supply the conductivity cell which is connected in series with a choke by means of a constant voltage source. Since the voltage source has low internal resistance, it will be apparent that the potential between the terminals of the conductivity cell remains approximately constant during slow changes in the impedance of the conductivity cell, whereas during pulse-like changes of this impedance there can be removed a voltage pulse at the terminals of the conductivity cell. With this solution the quiescent current in the particle free-conductivity cell can be directly adjusted by means of the voltage. However, such circuit is unstable in terms of the temperature, since temperature fluctuations cause corresponding uncontrollable current changes which can lead even to self-destruction of the circuit.